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Labor is a complex physiological process requiring a well-orchestrated dialogue between the mother and fetus. However, the cellular contributions and communications that facilitate maternal-fetal cross-talk in labor have not been fully elucidated. Here, single-cell RNA sequencing (scRNA-seq) was applied to decipher maternal-fetal signaling in the human placenta during term labor. First, a single-cell atlas of the human placenta was established, demonstrating that maternal and fetal cell types underwent changes in transcriptomic activity during labor. Cell types most affected by labor were fetal stromal and maternal decidual cells in the chorioamniotic membranes (CAMs) and maternal and fetal myeloid cells in the placenta. Cell-cell interaction analyses showed that CAM and placental cell types participated in labor-driven maternal and fetal signaling, including the collagen, C-X-C motif ligand (CXCL), tumor necrosis factor (TNF), galectin, and interleukin-6 (IL-6) pathways. Integration of scRNA-seq data with publicly available bulk transcriptomic data showed that placenta-derived scRNA-seq signatures could be monitored in the maternal circulation throughout gestation and in labor. Moreover, comparative analysis revealed that placenta-derived signatures in term labor were mirrored by those in spontaneous preterm labor and birth. Furthermore, we demonstrated that early in gestation, labor-specific, placenta-derived signatures could be detected in the circulation of women destined to undergo spontaneous preterm birth, with either intact or prelabor ruptured membranes. Collectively, our findings provide insight into the maternal-fetal cross-talk of human parturition and suggest that placenta-derived single-cell signatures can aid in the development of noninvasive biomarkers for the prediction of preterm birth. Editor's summary: Spontaneous labor involves complex communication between maternal and fetal cells, but our understanding of this cross-talk is limited. Here, Garcia-Flores and colleagues generated a single-cell atlas of the human placenta during term labor and performed cell-cell interaction analyses to better understand labor-driven maternal and fetal cell signaling changes. By combining their single-cell RNA-sequencing (RNA-seq) data with bulk RNA-seq datasets, they showed that placental signatures could be monitored in maternal blood during pregnancy and labor and that the signals in term labor were also present in cases of spontaneous preterm labor. Furthermore, signals were present in the blood of pregnant women who went on to experience spontaneous preterm birth, suggesting that it might be possible to develop tests to predict development of spontaneous preterm birth. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

Pregnancy represents a unique immunological state in which the mother adapts to tolerate the semi-allogenic conceptus; yet, the cellular dynamics in the maternal circulation are poorly understood. Using exon-level expression profiling of up to six longitudinal whole blood samples from 49 pregnant women, we undertook a systems biology analysis of the cellular transcriptome dynamics and its correlation with the plasma proteome. We found that: (1) chromosome 14 was the most enriched in transcripts differentially expressed throughout normal pregnancy; (2) the strongest expression changes followed three distinct longitudinal patterns, with genes related to host immune response (e.g., MMP8, DEFA1B, DEFA4 , and LTF) showing a steady increase in expression from 10 to 40 weeks of gestation; (3) multiple biological processes and pathways related to immunity and inflammation were modulated during gestation; (4) genes changing with gestation were among those specific to T cells, B cells, CD71+ erythroid cells, natural killer cells, and endothelial cells, as defined based on the GNF Gene Expression Atlas; (5) the average expression of mRNA signatures of T cells, B cells, and erythroid cells followed unique patterns during gestation; (6) the correlation between mRNA and protein abundance was higher for mRNAs that were differentially expressed throughout gestation than for those that were not, and significant mRNA-protein correlations were observed for genes part of the T-cell signature. In summary, unique changes in immune-related genes were discovered by longitudinally assessing the cellular transcriptome in the maternal circulation throughout normal pregnancy, and positive correlations were noted between the cellular transcriptome and plasma proteome for specific genes/proteins. These findings provide insights into the immunobiology of normal pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Fetal hypoxemia has been proposed to be one of the mechanisms of preterm labor (PTL) and delivery. This may have clinical implications since it may alter: (i) the method/frequency of fetal surveillance and (ii) the indications and duration of tocolysis to an already compromised fetus. The aim of this study was to examine whether there is a difference in the fetal blood gas analysis [pH, PaO2 and base excess (BE)] and in the prevalence of fetal acidemia and hypoxia between: (i) patients in PTL who delivered within 72 hours vs. those who delivered more than 72 hours after cordocentesis and (ii) patients with fetal inflammatory response syndrome (FIRS) vs. those without this condition. Study design: Patients admitted with PTL underwent amniocentesis and cordocentesis. Ninety women with singleton pregnancies and PTL were classified according to (i) those who delivered within 72 hours ( n = 30) and after 72 hours of the cordocentesis ( n = 60) and (ii) with and without FIRS. FIRS was defined as a fetal plasma concentration of IL-6 > 11 pg/mL. Fetal blood gases were determined. Acidemia and hypoxemia were defined as fetal pH and PaO2 below the 5th percentile for gestational age, respectively. For comparisons between the two study groups, ΔpH and ΔPaO2 were calculated by adjusting for gestational age (Δ = observed value - mean for gestational age). Non-parametric statistics were employed. Results: No differences in the median Δ pH (−0.026 vs. −0.016), ΔPaO2 (0.25 mmHg vs. 5.9 mmHg) or BE (−2.4 vs. −2.6 mEq/L) were found between patients with PTL who delivered within 72 hours and those who delivered 72 hours after the cordocentesis ( p > 0.05 for all comparisons). Fetal plasma IL-6 concentration was determined in 63% (57/90) of fetuses and the prevalence of FIRS was 28% (16/57). There was no difference in fetal pH, PaO2 and BE between fetuses with and without FIRS ( p > 0.05 for all comparisons). Moreover, there was no difference in the rate of fetal acidemia between fetuses with and without FIRS (6.3 vs. 9.8%; p > 0.05) and fetal hypoxia between fetuses with or without FIRS (12.5 vs. 19.5%; p > 0.05). Conclusions: Our data do not support a role for acute fetal hypoxemia and metabolic acidemia in the etiology of PTL and delivery. [ABSTRACT FROM AUTHOR]

Determines whether activation of the monocyte-neutrophil system occurs in fetuses before premature birth. Patient characteristics; Clinical and laboratory results; Neonatal outcomes; Activation marker results.

Compares the hematologic and biochemical values in cordocentesis specimens from twin pairs with and without stuck twin syndrome. Receiver-operator characteristic curve; Intertwin hemoglobin differences; Gestational age; Fetofetal transfusion syndrome; Placental pathology; Growth discordance; Estimated fetal weight.

Serum concentration of pancreatic oncofetal antigen (POA) was determined in human fetuses, newborns and pregnant women. The mean fetal concentration of POA (x = 5.27 μg/ml) changed very little with gestational age. Also, only a weak correlation was found between POA concentration of newborns (x = 5.15 μg/ml) and their birth weight. It appears that between the 19th and 40th weeks of gestation POA exhibits no fetospe-cific features, i.e. POA concentration did not exceed significantly the concentration of nonpregnant adults (x = 6.10 μg/ml). A number of pathophysiological variables was correlated with POA concentrations of newborns. The most striking statistical differences were found between American black and white newborns and adults; the mean concentration of POA in sera of black full-term newborns was 5.38 μg/ml as compared to white newborns, where the mean concentration was 3.58 μg/ml. Similarly, black mothers had a mean concentration (x = 12.21 μg/ml) significantly greater than white mothers (x = 5.62 μg/ml). Copyright © 1992 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: A sonographic short cervix (length <25 mm during midgestation) is the most powerful predictor of preterm birth. Current clinical practice assumes that the same cervical length cutoff value should apply to all women when screening for spontaneous preterm birth, yet this approach may be suboptimal.Objective: This study aimed to (1) create a customized cervical length standard that considers relevant maternal characteristics and gestational age at sonographic examination and (2) assess whether the customization of cervical length evaluation improves the prediction of spontaneous preterm birth.Study Design: This retrospective analysis comprises a cohort of 7826 pregnant women enrolled in a longitudinal protocol between January 2006 and April 2017 at the Detroit Medical Center. Study participants met the following inclusion criteria: singleton pregnancy, ≥1 transvaginal sonographic measurements of the cervix, delivery after 20 weeks of gestation, and available relevant demographics and obstetrical history information. Data from women without a history of preterm birth or cervical surgery who delivered at term without progesterone treatment (N=5188) were used to create a customized standard of cervical length. The prediction of the primary outcome, spontaneous preterm birth at <37 weeks of gestation, was assessed in a subset of pregnancies (N=7336) that excluded cases with induced labor before 37 weeks of gestation. Area under the receiver operating characteristic curve and sensitivity at a fixed false-positive rate were calculated for screening at 20 to 23 6/7, 24 to 27 6/7, 28 to 31 6/7, and 32 to 35 6/7 weeks of gestation in asymptomatic patients. Survival analysis was used to determine which method is better at predicting imminent delivery among symptomatic women.Results: The median cervical length remained fundamentally unchanged until 20 weeks of gestation and subsequently decreased nonlinearly with advancing gestational age among women who delivered at term. The effects of parity and maternal weight and height on the cervical length were dependent on the gestational age at ultrasound examination (interaction, P<.05 for all). Parous women had a longer cervix than nulliparous women, and the difference increased with advancing gestation after adjusting for maternal weight and height. Similarly, maternal weight was nonlinearly associated with a longer cervix, and the effect was greater later in gestation. The sensitivity at a 10% false-positive rate for prediction of spontaneous preterm birth at <37 weeks of gestation by a short cervix ranged from 29% to 40% throughout pregnancy, yet it increased to 50%, 50%, 53%, and 54% at 20 to 23 6/7, 24 to 27 6/7, 28 to 31 6/7, and 32 to 35 6/7 weeks of gestation, respectively, for a low, customized percentile (McNemar test, P<.001 for all). When a cervical length <25 mm was compared to the customized screening at 20 to 23 6/7 weeks of gestation by using a customized percentile cutoff value that ensured the same negative likelihood ratio for both screening methods, the customized approach had a significantly higher (about double) positive likelihood ratio in predicting spontaneous preterm birth at <33, <34, <35, <36, and <37 weeks of gestation. Among symptomatic women, the difference in survival between women with a customized cervical length percentile of ≥10th and those with a customized cervical length percentile of <10th was greater than the difference in survival between women with a cervical length ≥25 mm and those with a cervical length <25 mm.Conclusion: Compared to the use of a cervical length <25 mm, a customized cervical length assessment (1) identifies more women at risk of spontaneous preterm birth and (2) improves the distinction between patients at risk for impending preterm birth in those who have an episode of preterm labor. [ABSTRACT FROM AUTHOR]